Isolated hepatocyte suspensions and cultures are increasingly being used for in vitro toxicity and metabolism studies, but such studies are limited to animals the size of rodents because the perfusion methods used to release the cells from liver are not practical with larger animals. Recently, rat hepatocytes were isolated in this laboratory by a nonperfusion method. The research proposed in this application is designed to expand on this development further by comparing the metabolic disposition of drugs--e.g., imipramine, tolbutamide, amphetamine, diphenhydramine, indomethacin--using hepatocytes from several other species, including guinea pigs, rabbits, dogs, and squirrel monkeys to assess the potential utility of these cell preparations for comparative metabolism studies.